Approximately 324,000 people worldwide have received cochlear implants (CI), including children. The recent developments of bimodal electroacoustic devices and lowered age eligibility in children require long-term preservation of a patient's residual hearing and sensitive neural structures post-implantation. Mild therapeutic hypothermia is known to provide neuroprotection following ischemic and traumatic injuries. We have extended the application of localized hypothermia and applied it to the cochlea during electrode insertion. Our preliminary results suggest significant protection of hair cells from damage caused by insertion trauma and subsequent long-term protection of function. Localized hypothermia is beneficial over systemic hypothermia. In acute and chronic experiments, mild hypothermia (2-6C of cooling) achieved with a custom-designed thermoelectric cooling system and applied locally to the middle and basal turns of the cochlea was found to enable conservation of hearing. The overall objectives of the present application are to identify the inflammatory signaling events regulated by mild hypothermia after cochlear implantation and develop a clinical device to improve CI outcomes in patients. Acute and chronic studies in an animal model will guide future applications of therapeutic hypothermia. We will identify molecular pathways and gene networks together with single genes or gene families significant for otoprotection to further exploit benefits of hypothermia and improve its translation to clinica practice. The proposed studies will lead to the development of a clinical device and novel applications in preservation of auditory and vestibular function during neurotologic surgeries. Ensuring the survival of sensitive hair cells and neural structures in the cochlea will enable patients to benefit from future technologies and/or therapies.